[English] 日本語
Yorodumi
- PDB-6itm: Crystal structure of FXR in complex with agonist XJ034 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6itm
TitleCrystal structure of FXR in complex with agonist XJ034
Components
  • Bile acid receptor
  • HD3 Peptide from Nuclear receptor coactivator 1
KeywordsTRANSCRIPTION / FXR / agonist / non-alcoholic liver disease / docking screening
Function / homology
Function and homology information


regulation of urea metabolic process / chenodeoxycholic acid binding / positive regulation of phosphatidic acid biosynthetic process / positive regulation of glutamate metabolic process / positive regulation of ammonia assimilation cycle / regulation of low-density lipoprotein particle clearance / intracellular triglyceride homeostasis / cellular response to bile acid / negative regulation of very-low-density lipoprotein particle remodeling / negative regulation of interleukin-1 production ...regulation of urea metabolic process / chenodeoxycholic acid binding / positive regulation of phosphatidic acid biosynthetic process / positive regulation of glutamate metabolic process / positive regulation of ammonia assimilation cycle / regulation of low-density lipoprotein particle clearance / intracellular triglyceride homeostasis / cellular response to bile acid / negative regulation of very-low-density lipoprotein particle remodeling / negative regulation of interleukin-1 production / regulation of bile acid biosynthetic process / regulation of insulin secretion involved in cellular response to glucose stimulus / toll-like receptor 9 signaling pathway / negative regulation of monocyte chemotactic protein-1 production / nuclear receptor-mediated bile acid signaling pathway / bile acid nuclear receptor activity / bile acid metabolic process / labyrinthine layer morphogenesis / cell-cell junction assembly / positive regulation of transcription from RNA polymerase II promoter by galactose / regulation of thyroid hormone receptor signaling pathway / positive regulation of female receptivity / bile acid binding / cellular response to fatty acid / regulation of cholesterol metabolic process / negative regulation of interleukin-2 production / male mating behavior / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / hypothalamus development / intracellular glucose homeostasis / positive regulation of interleukin-17 production / negative regulation of interleukin-6 production / positive regulation of insulin secretion involved in cellular response to glucose stimulus / negative regulation of type II interferon production / cellular response to Thyroglobulin triiodothyronine / negative regulation of tumor necrosis factor production / Synthesis of bile acids and bile salts / negative regulation of tumor necrosis factor-mediated signaling pathway / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Endogenous sterols / fatty acid homeostasis / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / nuclear retinoid X receptor binding / progesterone receptor signaling pathway / response to retinoic acid / positive regulation of insulin receptor signaling pathway / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / histone H4K16 acetyltransferase activity / histone H3K56 acetyltransferase activity / histone H3K23 acetyltransferase activity / histone H2AK5 acetyltransferase activity / histone H2AK9 acetyltransferase activity / histone H2BK5 acetyltransferase activity / histone H2BK12 acetyltransferase activity / histone H3K4 acetyltransferase activity / histone H3K27 acetyltransferase activity / histone H3K36 acetyltransferase activity / histone H3K122 acetyltransferase activity / histone H3K18 acetyltransferase activity / histone H3K9 acetyltransferase activity / histone H3K14 acetyltransferase activity / histone H4K5 acetyltransferase activity / histone H4K8 acetyltransferase activity / histone H4K12 acetyltransferase activity / estrous cycle / cellular response to hormone stimulus / Recycling of bile acids and salts / negative regulation of canonical NF-kappaB signal transduction / histone acetyltransferase / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / estrogen receptor signaling pathway / Notch signaling pathway / positive regulation of adipose tissue development / : / lactation / Regulation of lipid metabolism by PPARalpha / peroxisome proliferator activated receptor signaling pathway / regulation of cellular response to insulin stimulus / cerebellum development / positive regulation of neuron differentiation / BMAL1:CLOCK,NPAS2 activates circadian expression / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / : / cholesterol homeostasis / hippocampus development / transcription coregulator binding / response to progesterone / nuclear receptor binding / nuclear estrogen receptor binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / SUMOylation of intracellular receptors / mRNA transcription by RNA polymerase II / Heme signaling / Transcriptional activation of mitochondrial biogenesis / euchromatin / PPARA activates gene expression / Cytoprotection by HMOX1 / cerebral cortex development / Nuclear Receptor transcription pathway
Similarity search - Function
Bile acid receptor, ligand binding domain / Thyroid hormone receptor / Nuclear receptor coactivator 1 / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator, Ncoa-type, interlocking / Nuclear receptor coactivator, Ncoa-type, interlocking domain superfamily / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator / DUF1518 / Nuclear receptor coactivator, receptor-binding domain ...Bile acid receptor, ligand binding domain / Thyroid hormone receptor / Nuclear receptor coactivator 1 / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator, Ncoa-type, interlocking / Nuclear receptor coactivator, Ncoa-type, interlocking domain superfamily / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator / DUF1518 / Nuclear receptor coactivator, receptor-binding domain / Nuclear receptor coactivator / Steroid receptor coactivator / Unstructured region on nuclear receptor coactivator protein / PAS domain / : / Nuclear receptor coactivator, interlocking / helix loop helix domain / Myc-type, basic helix-loop-helix (bHLH) domain / Myc-type, basic helix-loop-helix (bHLH) domain profile. / Helix-loop-helix DNA-binding domain superfamily / PAS fold / PAS fold / PAS domain / PAS repeat profile. / PAS domain / Retinoid X Receptor / Retinoid X Receptor / PAS domain superfamily / Nuclear hormone receptor / Nuclear hormones receptors DNA-binding region signature. / Zinc finger, nuclear hormone receptor-type / Double treble clef zinc finger, C4 type / Nuclear hormone receptors DNA-binding domain profile. / c4 zinc finger in nuclear hormone receptors / Nuclear hormone receptor, ligand-binding domain / Nuclear hormone receptor-like domain superfamily / Ligand-binding domain of nuclear hormone receptor / Nuclear receptor (NR) ligand-binding (LBD) domain profile. / Ligand binding domain of hormone receptors / Zinc finger, NHR/GATA-type / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-AWL / Nuclear receptor coactivator 1 / Bile acid receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å
AuthorsZhang, H. / Wang, Z.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China81603027 China
CitationJournal: J.Chem.Inf.Model. / Year: 2020
Title: Pose Filter-Based Ensemble Learning Enables Discovery of Orally Active, Nonsteroidal Farnesoid X Receptor Agonists.
Authors: Xia, J. / Wang, Z. / Huan, Y. / Xue, W. / Wang, X. / Wang, Y. / Liu, Z. / Hsieh, J.H. / Zhang, L. / Wu, S. / Shen, Z. / Zhang, H. / Wang, X.S.
History
DepositionNov 23, 2018Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Nov 27, 2019Provider: repository / Type: Initial release
Revision 1.1Jun 10, 2020Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Nov 22, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ncs_dom_lim
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Bile acid receptor
B: HD3 Peptide from Nuclear receptor coactivator 1
C: Bile acid receptor
D: HD3 Peptide from Nuclear receptor coactivator 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)60,2246
Polymers59,4784
Non-polymers7462
Water59433
1
A: Bile acid receptor
B: HD3 Peptide from Nuclear receptor coactivator 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)30,1123
Polymers29,7392
Non-polymers3731
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1120 Å2
ΔGint-5 kcal/mol
Surface area11810 Å2
MethodPISA
2
C: Bile acid receptor
D: HD3 Peptide from Nuclear receptor coactivator 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)30,1123
Polymers29,7392
Non-polymers3731
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1130 Å2
ΔGint-3 kcal/mol
Surface area12060 Å2
MethodPISA
Unit cell
Length a, b, c (Å)101.484, 130.192, 37.654
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11chain A
21(chain C and (resid 258 through 469 or resid 473 through 485 or resid 501))
12chain B
22chain D

NCS domain segments:
Dom-IDComponent-IDEns-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
111GLUGLUVALVALchain AAA258 - 48512 - 239
211GLUGLUARGARG(chain C and (resid 258 through 469 or resid 473 through 485 or resid 501))CC258 - 46912 - 223
221HISHISVALVAL(chain C and (resid 258 through 469 or resid 473 through 485 or resid 501))CC473 - 485227 - 239
231AWLAWLAWLAWL(chain C and (resid 258 through 469 or resid 473 through 485 or resid 501))CF501
112ASPASPASPASPchain BBB2 - 132 - 13
212ASPASPASPASPchain DDD2 - 132 - 13

NCS ensembles :
ID
1
2

-
Components

#1: Protein Bile acid receptor / Farnesoid X-activated receptor / Farnesol receptor HRR-1 / Nuclear receptor subfamily 1 group H ...Farnesoid X-activated receptor / Farnesol receptor HRR-1 / Nuclear receptor subfamily 1 group H member 4 / Retinoid X receptor-interacting protein 14 / RXR-interacting protein 14


Mass: 27949.084 Da / Num. of mol.: 2 / Mutation: E281A, E354A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NR1H4, BAR, FXR, HRR1, RIP14 / Plasmid: pRHisMBP / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q96RI1
#2: Protein/peptide HD3 Peptide from Nuclear receptor coactivator 1 / SRC-1 HD3


Mass: 1790.026 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q15788, histone acetyltransferase
#3: Chemical ChemComp-AWL / 1-adamantyl-[4-(5-chloranyl-2-methyl-phenyl)piperazin-1-yl]methanone


Mass: 372.931 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C22H29ClN2O / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 33 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.09 Å3/Da / Density % sol: 41.18 % / Mosaicity: 0.442 ° / Mosaicity esd: 0.006 °
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 6.5
Details: 0.2M Ammonium acetate, 0.1M Bis-Tris pH 6.5, 25% w/v Polyethylene glycol 3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL17U1 / Wavelength: 0.97894 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Nov 11, 2018
RadiationMonochromator: double crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97894 Å / Relative weight: 1
ReflectionResolution: 2.5→50 Å / Num. obs: 18007 / % possible obs: 99.8 % / Redundancy: 8.9 % / Rmerge(I) obs: 0.06 / Rpim(I) all: 0.021 / Rrim(I) all: 0.064 / Χ2: 0.937 / Net I/σ(I): 10.8 / Num. measured all: 159545
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
2.5-2.598.80.8317410.770.2970.8830.94399.8
2.59-2.699.30.60317920.8960.210.6390.9799.9
2.69-2.829.40.41917360.9430.1460.4450.93799.9
2.82-2.969.20.28917640.9730.1010.3070.96899.8
2.96-3.1590.18317980.9850.0650.1950.95499.9
3.15-3.398.80.10617830.9930.0380.1130.96599.9
3.39-3.737.90.06617840.9960.0240.070.97199.3
3.73-4.279.30.04218000.9980.0140.0440.938100
4.27-5.3890.03418560.9980.0120.0360.9499.9
5.38-507.90.02819530.9990.010.030.77499.8

-
Processing

Software
NameVersionClassification
PHENIX1.14_3260refinement
DENZOdata reduction
SCALEPACKdata scaling
PDB_EXTRACT3.24data extraction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4QE6

4qe6
PDB Unreleased entry


Resolution: 2.5→47.278 Å / SU ML: 0.27 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 24.78 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2418 870 5 %RANDOM
Rwork0.1918 16524 --
obs0.1943 17394 96.58 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 140.89 Å2 / Biso mean: 45.246 Å2 / Biso min: 11.17 Å2
Refinement stepCycle: final / Resolution: 2.5→47.278 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3919 0 52 33 4004
Biso mean--66.18 34.47 -
Num. residues----477
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDNumberRefine-IDRmsType
11A2168X-RAY DIFFRACTION9.663TORSIONAL
12C2168X-RAY DIFFRACTION9.663TORSIONAL
21B122X-RAY DIFFRACTION9.663TORSIONAL
22D122X-RAY DIFFRACTION9.663TORSIONAL
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.5005-2.65710.31431260.236224381
2.6571-2.86230.29361310.2235278499
2.8623-3.15020.2831560.21762804100
3.1502-3.6060.24521630.19952795100
3.606-4.54250.22391410.17062876100
4.5425-47.2780.20121530.1743022100
Refinement TLS params.Method: refined / Origin x: 35.0296 Å / Origin y: 16.1117 Å / Origin z: 9.5404 Å
111213212223313233
T0.1772 Å20.0373 Å2-0.0018 Å2-0.1535 Å2-0.0351 Å2--0.1156 Å2
L1.9026 °20.6075 °20.1515 °2-0.4046 °2-0.0333 °2--0.0653 °2
S-0.0199 Å °-0.0379 Å °-0.1011 Å °0.0258 Å °0.0358 Å °-0.0991 Å °0.0071 Å °-0.0038 Å °-0.0099 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1allA258 - 485
2X-RAY DIFFRACTION1allA501
3X-RAY DIFFRACTION1allB2 - 13
4X-RAY DIFFRACTION1allC258 - 485
5X-RAY DIFFRACTION1allC501
6X-RAY DIFFRACTION1allD2 - 13
7X-RAY DIFFRACTION1allS1 - 33

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more